Environmental agents with estrogen-like activity are a major public health issue. Although a variety of assays have been developed to detect binding to the estrogen receptor (ER) and other assays have been developed to monitor subsequent effects on estrogen sensitive gene transcription, an Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) recently reported difficulties with all available methods. We are developing quartz crystal microbalance (QCM) platform technology for the quantitative high-throughput analysis of complex macromolecular interactions. The focus of this project is the development of QCM biosensors for rapid quantification of the influence of endocrine disrupters on the interactions among the estrogen receptor (ER), coactivators or corepressors and the estrogen response element (ERE). QCM has been applied to study interactions of proteins with small molecules, protein-protein interactions, and DMA hybridization. It is expected that QCM will provide heretofore inaccessible quantitative information regarding effects of endocrine disrupters on the kinetics and affinity of the ER for the ERE as well as comparable information about the influence of endocrine disrupters on interactions between the ER and coactivators, corepressors, and other transcription factors whose interactions regulate estrogen-responsive genes in many cell types and organisms. Major advantages of QCM include high sensitivity, low cost, real time label-free, quantitative analysis. Given the U.S. congressional mandate and World Health Organization recommendations for endocrine disrupter testing of chemicals, we anticipate strong market demand for ERE biosensor technology.